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Resolving mRNA loading heterogeneity in lipid nanoparticles: a single-particle Raman spectroscopy approach.
Rel. Clara Mattu, Luca Panariello. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2026
Abstract
Nucleic acid drugs, especially messenger RNA (mRNA), are at the forefront of modern therapeutic strategies. These drugs require the use of advanced formulations, such as lipid nanoparticles (LNPs), to overcome biological barriers and protect them against enzymatic degradation. Although these systems have been clinically validated, their physicochemical characterisation is challenging because there is a fraction of empty particles that increase the heterogeneity of the final product. Average information about the population is provided by conventional bulk analysis techniques, such as Dynamic Light Scattering and RiboGreen fluorescence assays; however, these methods cannot resolve compositional differences between individual particles. In this thesis work, SPARTA (Single Particle Automated Raman Trapping Analysis) technology was used to analyse single nanoparticles and map the loading heterogeneity of mRNA.
Two different clinically-approved formulations based on different ionizable lipids were compared: SM-102 (Moderna) and Dlin-MC3-DMA (Onpattro)
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